Inflammatory bowel disease is a recurrent chronic intestinal inflammatory disease with unknown etiology and no effective treatment. Phosphodiesterase (PDE) regulates a variety of physiological and pathophysiological processes by mediating the hydrolysis of intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. In recent years, a series of researches suggest that PDE inhibitors such as several PDE4 inhibitors, PDE5 inhibitors (sildenafil, tadalafil and vardenafil), PDE3 inhibitors (cilostazol), PDE9 inhibitor (PF-04447943) and PDE3/PDE4 double inhibitor (pumafentrine) have ameliorating effect on experimental colitis in animals. In clinical trials, PDE4 inhibitor apremilast showed more therapeutic advantage than tetomilast. This article reviews the recent research progress of PDE inhibitors in treatment of inflammatory bowel disease.
Animals ; Colitis ; Inflammatory Bowel Diseases/drug therapy* ; Phosphodiesterase 4 Inhibitors

Humans ; Inflammatory Bowel Diseases/drug therapy* ; Interleukin-6/therapeutic use*

Traditional medications used for treating autoimmune diseases often come with a wide range of adverse effects. Current treatments focus mainly on symptom management, resulting in significant health issues and financial burdens for patients. Recently, clinical research has demonstrated the potential of helminths and their derivatives as effective therapies for autoimmune disorders. Helminths, being a near-natural immunomodulator, exhibit milder effects than broad-spectrum immunosuppressants and corticosteroids, thereby presenting a promising alternative for the treatment of autoimmune diseases. However, different helminths' therapeutic efficacy and mechanisms and their derivatives in treating autoimmune diseases may vary. Therefore, we aim to review recent clinical advancements in the use of helminths and their derivatives for treating inflammatory bowel disease, multiple sclerosis, and autism spectrum disorder, with a view to offering novel clinical treatment approaches.
Animals ; Humans ; Autism Spectrum Disorder ; Autoimmune Diseases/drug therapy* ; Helminths ; Inflammatory Bowel Diseases

Inflammatory bowel disease(IBD) is a chronic and recurrent inflammatory disorder of the gut, including Crohn's disease(CD) and ulcerative colitis(UC). The occurrence and development of IBD involves multiple pathogenic factors, and the dybiosis of gut flora is recognized as an important pathogenic mechanism of IBD. Therefore, restoring and maintaining the balance of gut flora including bacteria and fungi has become an effective option for IBD treatment. Based on the theoretical basis of the interaction between gut flora and IBD, this paper followed the principle of clinical syndrome differentiation for IBD therapy by traditional Chinese medicine(TCM), and summarized several Chinese medicinal formulae commonly used in IBD patients with large intestine damp-heat syndrome, intermingled heat and cold syndrome, spleen deficiency and dampness accumulation syndrome, spleen and kidney yang deficiency syndrome, liver stagnation and spleen deficiency syndrome, and severe heat poisoning syndrome. The therapeutic and regulatory effects of Shaoyao Decoction, Qingchang Suppository, Wumei Pills, Banxia Xiexin Decoction, Shenling Baizhu Powder, Lizhong Decoction, Sishen Pills, Tongxie Yaofang, Baitouweng Decoction, Gegen Qinlian Decoction, and Houttuyniae Herba prescriptions on gut flora of IBD patients were emphasized as well as the mechanisms. This study found that Chinese medicinal formulae increased the abundance of Bacteroidetes, Bifidobacteria, Lactobacillus, and other beneficial bacteria producing short-chain fatty acids, and reduced the abundance of Enterobacteriaceae and other harmful bacteria to restore the balance of gut flora, thus treating IBD. Confronting the recalcitrance and high recurrence of IBD, Chinese medicinal formulae provide new opportunities for IBD treatment through intervening dysbiosis of gut flora.
Humans ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/drug therapy* ; Dysbiosis/drug therapy* ; Colitis, Ulcerative/drug therapy* ; Bacteria/genetics* ; Homeostasis ; China

The efficacy of conventional drug therapy for inflammatory bowel disease (IBD) is not satisfactory. As monoclonal antibody has been widely used and increasingly understood, biological agent therapy has been proved as ideal strategy in attaining mucosal healing, preventing complications, improving quality of life, and reducing hospitalization and surgical intervention. Furthermore, different randomized clinical trials assessed the efficacy in reducing the need for repeat surgery because of recurrence. Besides, biological agent therapy dose not increase most of postoperative side effects such as infection. However, adverse events of biological agents including serious infection, infusion reactions, delay type allergic reaction and myelosuppression should be paid attention to.
Biological Products ; adverse effects ; therapeutic use ; Humans ; Inflammatory Bowel Diseases ; drug therapy

Inflammatory bowel disease(IBD) is a non-specific and chronic recurrent autoimmune disease that involves the gastrointestinal tract. Clinical symptoms of intestinal bleeding, diarrhea, and weight loss threat to human health and induce colorectal cancer. The pathogenesis included living environment, genetic factors, immune cell infiltration and immune stress, weakened mucosal barrier defense and intestinal flora imbalance. At present, clinical treatment drugs mainly include aminosalicylic acid, corticosteroids, immunosuppressants, biological agents, etc., in view of the disadvantages of poor therapeutic effect and expensive price. The active ingredients of traditional Chinese medicine(TCM) in the treatment IBD have various biological activities and multiple targets such as anti-inflammatory, antibacterial, anti-tumor and immune regulation. This article summarized the application and the research progress in protecting intestinal epithelial barrier, maintaining intestinal microbial homeostasis, inhibiting causative factors, and regulating Th1/Th17/Treg balance about TCM in the treatment of IBD. The review provided new ideas for further development of the new drugs on the mechanism based on active ingredients of TCM in IBD treatment.
Humans ; Inflammatory Bowel Diseases ; therapy ; Intestinal Mucosa ; drug effects ; physiopathology ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.
Animals ; Zebrafish ; Lipopolysaccharides ; Disease Models, Animal ; Inflammatory Bowel Diseases/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Trinitrobenzenesulfonic Acid/adverse effects* ; Colitis/drug therapy*

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Accordingly, the duration and anatomic extent of the disease have been known to affect the development of IBD-related CRC. When CRC occurs in patients with IBD, unlike in sporadic CRC, it is difficult to detect the lesions because of mucosal changes caused by inflammation. In addition, the tumor types vary with ill-circumscribed lesions, and the cancer is difficult to diagnose and remedy at an early stage. For the diagnosis of CRC in patients with IBD, screening endoscopy is recommended 8 to 10 years after the IBD diagnosis, and surveillance colonoscopy is recommended every 1 to 2 years thereafter. The recent development of targeted biopsies using chromoendoscopy and relatively newer endoscopic techniques helps in the early diagnosis of CRC in patients with IBD. A total proctocolectomy is advisable when high-grade dysplasia or multifocal low-grade dysplasia is confirmed by screening endoscopy or surveillance colonoscopy or if a nonadenoma-like dysplasia-associated lesion or mass is detected. Currently, pharmacotherapies are being extensively studied as a way to prevent IBD-related CRC.
Biopsy ; Chemoprevention ; Colonic Neoplasms* ; Colonoscopy ; Colorectal Neoplasms ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Endoscopy ; Humans ; Inflammation ; Inflammatory Bowel Diseases* ; Mass Screening*

Thiopurine S-methyltransferase (TPMT) methylates purine analogues, showing TPMT activity in inverse relation to concentrations of active metabolites such as 6-thioguanine nucleotide (6-TGN). With conventional dosing of thiopurines, patients with homozygous variant TPMT alleles consistently suffer from severe myelosuppression. Here, we report a patient with TPMT*3C/*3C who managed successfully with monitoring of thiopurine metabolites. The patient was an 18-year-old male diagnosed with Crohn's disease. The standard dose of azathioprine (AZA) (1.8 mg/kg/day) with mesalazine (55.6 mg/kg/day) was prescribed. Two weeks after starting AZA treatment, the patient developed leukopenia. The DNA sequence analysis of TPMT identified a homozygous missense variation (NM_000367.2: c.719A>G; p.Tyr240Cys), TPMT*3C/*3C. He was treated with adjusted doses of azathioprine (0.1-0.2 mg/kg/day) and his metabolites were closely monitored. Leukopenia did not reoccur during the follow-up period of 24 months. To our knowledge, this is the first case of a patient homozygous for TPMT*3C successfully treated with azathioprine in Korea. While a TPMT genotyping test may be helpful to determine a safe starting dose, it may not completely prevent myelosuppression. Monitoring metabolites as well as routine laboratory tests can contribute to assessing drug metabolism and optimizing drug dosing with minimized drug-induced toxicity.
Adolescent ; Azathioprine/adverse effects/*therapeutic use ; Homozygote ; Humans ; Inflammatory Bowel Diseases/*drug therapy/*enzymology/*genetics/metabolism ; Male ; Methyltransferases/*genetics

BACKGROUNDS: Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD) increased prevalence and economic burden. OBJECTIVES: This study aimed to investigate drug use pattern in IBD patients in a real world. METHODS: National Health Insurance claim data from 2010 to 2014 were used in this population-based study. All IBD patients diagnosed during study period were enrolled. IBD medications included 5-aminosalicylic acid (ASA), glucocorticoid, immunomodulator and anti-tumor necrosis factor-α agent(anti TNF-α). Growth rate of IBD prevalence, prescribed drug classes, duration of drug therapy and medication cost were analyzed. Number and percentage of patients for categorical variables, and mean and median for continuous variables were presented. RESULTS: Total numbers of patients were 131,158 and 57,286 during 5 years, and their annual growth rate were 3.2 and 5.7% for UC and CD. UC and CD were prevalent in the 40–50 (41.2%) and 20–30 age groups (36.0%). About 60% of IBD patients was prescribed any of medications. 5-ASA was the most frequently prescribed, followed by corticosteroid and immunomodulator. Anti TNF-α use was the lowest, but 5 times higher than UC in CD. Combination therapies with different class of drugs were in 29% for UC and 62% for CD. Mean prescription days per patient per year were 306 and 378, and the median medication cost per patient per year was KRW 420,000 (USD 383) and KRW 830,000 (USD755), for UC and CD, respectively. CONCLUSIONS: Increasing prevalence of IBD requires further studies to contribute to achieve better clinical outcomes of drug therapy.
Colitis, Ulcerative ; Crohn Disease ; Drug Therapy ; Health Expenditures ; Humans ; Inflammatory Bowel Diseases ; Mesalamine ; National Health Programs ; Necrosis ; Prescriptions ; Prevalence